The research objectives include investigations to elucidate the underlying mechanisms involved in defective collagen maturation in a heritable connective tissue disease of dogs, the Ehlers-Danlos syndrome (ED-S), which is a homolog of the ED-S of man. These objectives include defining the biochemical lesion and molecular defect with particular emphasis on intermolecular collagen cross-linking and the mechanism of formation of cross-links. Methods to be employed include extraction, separation, and isolation of connective tissue components, and examination of collagen cross-linking and intrinsic and extrinsic factors involved in the cross-linking phenomena by use of chromatographic techniques, amino acid analyses, electrophoresis, peptide fingerprinting, and spectrophotometry. In addition, it is the objective of this study to correlate the biochemical lesion with structural and functional changes as they relate to the disease process and aging in the entire animal. This will be accomplished by relating the biochemical lesion to morphologic alteration, including histologic, ultrastructural, and radiologic changes, and to mechanical changes in the involved tissues. Furthermore, it is the objective of this study to provide a basis for a more thorough understanding of the basic defect in the Ehlers-Danlos syndrome of man and to provide insight into mechanisms by which alterations in connective tissue in aging and disease processes of man may occur.